title: Lactoferrin enhances hydroxyl radical production by human neutrophils, neutrophil particulate fractions, and an enzymatic generating system.
abstract: During phagocytosis, neutrophils take oxygen from the surrounding medium and convert it to superoxide anion (O2-) and hydrogen peroxide (H2O2). Hydroxyl radical (.OH), a particularly potent oxidant, is believed to be produced by interaction between O2- and H2O2 in the presence of iron, according to the Haber-Weiss reactions. Production of .OH by whole human neutrophils, by particulate fractions from human neutrophils disrupted after stimulation, and by a xanthine oxidase system was measured by conversion of alpha-keto-gamma-methiol butyric acid to ethylene. FeCl3 or ferric EDTA enhanced ethylene production in all three systems by 155--406% of base line at a concentration of 50--100 microM. Iron-saturated human milk lactoferrin, 100 nM, increased ethylene generation by 127--296%; and purified human neutrophil lactoferrin, 10 nM, enhanced ethylene production by 167--369%. Thus, iron bound to lactoferrin was approximately 5,000 times more effective in producing an enhancement in ethylene generation than iron derived from FeCl3 or ferric EDTA. O2- and H2O2 were required for ethylene production in the presence of lactoferrin, since superoxide dismutase inhibited ethylene formation in the three systems by 76--97% and catalase inhibited by 76--98%. Ethylene production in the presence of lactoferrin was inhibited by the .OH scavengers mannitol, benzoate, and thiourea by 43--85, 45--94, and 76--96%, respectively. Thus, most of the ethylene production could be attributed to oxidation of alpha-keto-gamma-methiol butyric acid by .OH. The ability of neutrophil lactoferrin to provide iron efficiently to the oxygen radical-generating systems is compatible with a role for lactoferrin as regulator of .OH production. As such, lactoferrin may be an important component in the microbicidal activity of neutrophils.
mesh_terms: D001565:Benzoates / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D005030:Ethylenes / Q000096:biosynthesis; D005609:Free Radicals; D006801:Humans; D006878:Hydroxides / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D007781:Lactoferrin / Q000494:pharmacology*; D007782:Lactoglobulins / Q000494:pharmacology*; D008353:Mannitol / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010587:Phagocytosis; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013890:Thiourea / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D001565:Benzoates; D005030:Ethylenes; D005609:Free Radicals; D006878:Hydroxides; D007782:Lactoglobulins; D012710:Serum Albumin, Bovine; D008353:Mannitol; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D007781:Lactoferrin; D013890:Thiourea